In this program, clinicians and basic scientists study structure and function in the auditory pathway in animals and humans. The projects target clinical and basic-science issues from the middle and inner ear, through brainstem to cortex, in normal and hearing impaired individuals. Engineering, physiological and clinical approaches are combined in Project 1 to study conductive hearing loss in humans. Using measurements in human temporal bones to test models of sound transmission, the efficacies of surgical techniques are predicted and predictions tested against clinical outcomes. Biological and engineering approaches are combined in Project 2 to investigate the role of cochlear supporting cells in maintaining ion balance in normal and high-level sound environments. If our hypotheses are correct, malfunction in this supporting-cell network may lead to cochlear fluid disorders, and understanding their normal function may suggest effective treatments. Another team combines pharmacology, physiology and molecular biology, in Project 3, to prove the molecular mechanisms underlying efferent protection of the inner ear from acoustic injury. Our hypotheses suggest a number of drugs which should enhance protection and also suggest a novel cell-signaling system of general importance to cell biology. The cochlear efferent pathway may also improve auditory performance in noisy environments. The functional role of this feedback pathway is investigated in Project 4, by assaying efferent-reflex strength in human subjects as the auditory task changes to resolve whether up-or down-regulation of this reflex occurs. In Project 5, neurophysiology, psychophysics and neuroanatomy combine to investigate the neural substrate for perceptual phenomena in spatial hearing, such as the improved detectability of masked signals as signal and noise sources are spatially separated. Insight into the underlying physiological mechanisms is important in understanding performance deficits in the hearing impaired, especially in noisy environments. Project 6 studies auditory processing in human subjects via functional magnetic resonance imaging (fMRI) of neuronal activity. Advances in fMRI enable resolution of localized activation throughout the auditory pathway from cochlear nucleus to cortex, allowing this team of basic scientists and clinicians to directly test fundamental and longstanding assumptions concerning the applicability of neurophysiological studies of animal models to human audition, in normal and hearing impaired individuals.